Hassani Idrissi Hind, Hmimech Wiam, Khorb Nada El, Akoudad Hafid, Habbal Rachida, Nadifi Sellama
Laboratory of Genetics and Molecular Pathology, Medical School, University Hassan II, Casablanca, Morocco.
Department of Cardiology, University Hospital Center Hassan II, Fes, Morocco.
BMC Res Notes. 2018 Jan 18;11(1):46. doi: 10.1186/s13104-018-3132-0.
The main objective of our study was to investigate the association of CYP2C192 and CYP2C193 loss-of-function and CYP2C19*17 gain-of-function variants of CYP2C19 gene with Clopidogrel resistance in a sample of Moroccan Acute Coronary Syndromes patients.
Our results showed the existence of a synergic effect between the three alleles, statistically very significant, on Clopidogrel resistance among the treated patients (P = 0.0033). For the three variants of the CYP2C19 gene, the heterozygous and homozygous mutant genotypes were the most frequent among ACS patients (CYP2C192: 82.76% GA and 10.35% AA; CYP2C193: 76.67% GA and 18.33% AA; CYP2C1917: 66.67% CT and 18.66% TT). Allelic frequencies were 51.73% vs 48.27% (P < 0.001); 56.67% vs 43.33% (P < 0.001); and 52% vs 48% (P = 0.01) for the mutant and wild type alleles of the CYP2C192, CYP2C193 and CYP2C1917 variants respectively. Our results support a role of CYP2C19 gene variants as a potential marker of Clopidogrel response. Understanding the functional and clinical consequences of these variants may help for treating patients more effectively, they could be genetically screened and appropriate dose adjustments could be made on the basis of their CYP2C19 genotype.
我们研究的主要目的是在一组摩洛哥急性冠脉综合征患者样本中，调查细胞色素P450 2C19（CYP2C19）基因的功能缺失型CYP2C192和CYP2C193以及功能增强型CYP2C19*17变异与氯吡格雷抵抗之间的关联。
我们的结果显示，在接受治疗的患者中，这三个等位基因之间存在协同效应，对氯吡格雷抵抗具有统计学意义上的显著影响（P = 0.0033）。对于CYP2C19基因的三种变异，杂合子和纯合子突变基因型在急性冠脉综合征患者中最为常见（CYP2C192：82.76%为GA，10.35%为AA；CYP2C193：76.67%为GA，18.33%为AA；CYP2C1917：66.67%为CT，18.66%为TT）。CYP2C192、CYP2C193和CYP2C1917变异的突变型和野生型等位基因的等位基因频率分别为51.73%对48.27%（P < 0.001）；56.67%对43.33%（P < 0.001）；以及52%对48%（P = 0.01）。我们的结果支持CYP2C19基因变异作为氯吡格雷反应潜在标志物的作用。了解这些变异的功能和临床后果可能有助于更有效地治疗患者，可以对患者进行基因筛查，并根据其CYP2C19基因型进行适当的剂量调整。
